Thursday, December 18, 2014

Trypanosoma cruzi

By Noora Hussain

The
human body has an army at the ready to attack and protect itself from invaders.
This army is called the immune system. It is equipped with weapons that span
the physical body, are effective against many different types of attacks, and
are organized in such a way that allows for strategic interactions which
amplifies the body’s defenses. When a parasite wages war on the body, the
body’s army goes into battle with full force. Winning results in successful
elimination of the parasite from the body, but may leave the immune system
weakened. Losing the battle can result in disease. Parasites have their own
arsenal of weapons, which allows them to defeat the immune system. Parasites
have mechanisms that shield them from host’s defenses and have ways to attack
specific target cells. One such parasite that wields its own sword and shield
is Trypanosoma cruzi. This motile protozoan
pathogen is the causative agent of Chagas disease.1 Chagas disease
affects the cardiac and digestive systems of the body and can cause acute or
chronic infections2.The
parasite T. cruzi uses offensive
mechanisms to counterattack a host cell’s defenses.

Chagas
disease affects eight million people in Latin America.2 The disease
was discovered in 1909 by the Brazilian physician Carlos Chagas, who named the
parasite after his mentor Oswaldo Cruz.3 Chagas disease can cause
acute or chronic infection that affects many different cells of the body.2
Clinical manifestations of acute infections include myocarditis,
pericardial effusion, or meningoencephalitis.3 After the initial
acute stage subsides, the diseases enters the chronic stage.3 Most
patients can survive with the chronic infection, but a small percentage of
patients develop cardiomyopathies within a year.3 Infection by T. cruzi occurs in a cycle and involves
blood sucking insect vectors belonging to the Reduviidae family. 4 From the insect, the parasite comes
into contact with a human or a wild animal.2 Then, it goes back to
the insect when the insect feeds off the infected human.2 When the
blood sucking insect lands on skin to feed, it also defecates in that spot
leaving behind T. cruzi infected
feces.5 Fecal droplets can get passed inside of humans through
mucosa or through breaks in the epithelial barrier.5T. cruzi can also infect through oral
transmission with infected foods.5 Another much less common
transmission mechanism is from blood transfusion.5 Congenital
transmission from infected mother to child is also possible, but like blood
transfusions is not a very common mechanism.5

Trypomastigotes
are the infectious forms of T. cruzi
and they infect the endothelial and mucosal cells of humans and other mammals.6
They invade these cells in order to differentiate and replicate inside of the
host cell lysosome and cytoplasm.6 The invasion mechanism of T. cruzi is unique because it uses the
host cell machinery that would generally be used against a protozoan parasite. T. cruzi trypomastigotes are highly
motile7. A flagellum is attached to the cell body of T. cruzi, which enables the parasite to
move on its own.8 Active motility of T. cruzi is a mechanism that the parasite uses to penetrate through
the host cell membrane.9 After it gains entry, the host cell is
infected.9 Once the host cell is infected, the trypomastigotes
undergo cytokinesis, but their nuclei do not divide.9 The division
occurs towards the back end of the basal body where the flagellum is attached.9
Through this process, the unnecessary flagellum is discharged into the host
cell cytoplasm where it is then degraded.9

The
surface of T. cruzi provides a shield
for the parasitic pathogen. This enables the parasite to travel throughout the
body without being defenseless against the host’s immune system. The major
surface components of T.cruzi provide
the parasite with protection against the host’s cell defenses and enables the
parasite to adhere to specific target cells for invasion.5 Mucin is
a glycoprotein and one of the major surface components that plays a role in
infection.1 Mucin sticks out from the outer phospholipid layer of T. cruzi’s plasma membrane.5
They are anchoredto the plasma membrane
by glycosylphosphatidylinositol (GPI).1 These GPI-anchored
glycoproteins cover the majority of the T.
cruzi’s surface.5 Mucins recognize and target endothelial cells
for invasion.5They attach
themselves onto the lipid bilayer of host cells.10 A signal is
transduced that directs the glycoprotein into the cytoplasm and to the
endoplasmic reticulum of the host cell.10 Once inside the host cell,
T. cruzi can also interact with other
organelles in the cytoplasm and use them to mediate infection.10

Host
cells have lysosomes to remove unwanted material from inside of their cells.
Normally, a lysosome would ingest, destroy, and secrete an invading pathogen.
However, upon infection, T. cruzi’s
plasma membrane fuses with the host cell lysosome, creating what is called a
lysosome derived parasitophorous vacuole.6 The formation of the
parasitophorous vacuole anchors the parasite to a structure of the host.6
The anchored parasite can undergo replication before disseminating into the
host’s bloodstream and throughout the body.6T. cruzi interacts with lysosomes of thehost cell because they have a low pH value.6Having a highly acid organelle is a
defense weapon of the host, but is used against the host when it facilitates trypomastigotes
differentiation, replication, and dissemination.6 The
parasitophorous vacuole membrane is disrupted and the acidic environment can
have its full effect on the trypomastigotes.6Disruption of the membrane is caused by the
release of the pore forming molecule TcTox from trypomastigotes.6 Release
of this molecule is triggered by the lysosome’s acid environment.6Acidity also serves as a trigger to initiate
differentiation of trypomastigotes into amastigotes.6 Amastigotes
replicate, exit the lysosome, and disseminate into the blood stream.3
This spreads infection to other cells of the body.3-6

The outcome of a battle between a
parasite and the human body is critically important. A human’s immune system is
well equipped to defend against many infections. However, parasites have
developed mechanisms that provide them with a good offense and can retaliate
against the immune system. So, in a battle between the two, the immune system
does not always defeat the invader and the parasite can conquer and win.

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This blog represents the work of students from one of the few courses devoted to Eukaryotic Microbiology as a whole. This is a new experiment for this course that we hope will be a successful fusion of student learning and science communication. Enjoy, but play nice, comments are welcome but mean-spirited comments will be deleted.